Hydrochloric Acid → 5-(Methanesulfonylamino-methyl)-thiophen-2-yl-acetic acid methyl ester

HRID 480356

반응식

HRID 480356 반응식
[CH3:1][O:2][C:3](=[O:10])[CH2:4][C:5]1[S:6][CH:7]=[CH:8][CH:9]=1.Cl.[CH2:12]=O.[CH3:14][S:15]([NH2:18])(=[O:17])=[O:16]>O1CCOCC1.[Cl-].[Zn+2].[Cl-].CCOC(C)=O>[CH3:1][O:2][C:3](=[O:10])[CH2:4][C:5]1[S:6][C:7]([CH2:12][NH:18][S:15]([CH3:14])(=[O:17])=[O:16])=[CH:8][CH:9]=1

참가 물질

8

반응물 4

HCID 313Hydrochloric AcidHCID 712FormaldehydeHCID 72879MethanesulfonamideHCID 88055Methyl thiophen-2-acetate

생성물 1

HCID 544573365-(Methanesulfonylamino-methyl)-thiophen-2-yl-acetic acid methyl ester수율 69%

시약·촉매·용매 3

HCID 3007855Zincchloride촉매HCID 8857Ethyl Acetate용매HCID 312751,4-Dioxane용매

실험 절차

To a solution of thiophen-2-yl-acetic acid methyl ester (2 mL, 12.8 mmol) in 1,4-dioxane (10 mL) was added concentrated HCl (0.4 mL, 4.8 mmol) dropwise over 10 minutes. Zinc chloride (78 mg, 0.57 mmol) was added and the reaction was lowered into a pre-heated water bath at 45° C. and was stirred for 15 minutes. HCl (g) was bubbled into the solution for 2-3 minutes. The temperature of the reaction rose to about 60° C. Upon cooling, 37% aqueous formaldehyde (1.24 mL, 16 mmol) was added dropwise and the temperature rose to 70° C. The reaction was cooled to room temperature and methanesulfonamide (1.25 g, 12.8 mmol) was added in portions. The reaction was stirred for 3 h and was poured into EtOAc (60 mL). The organic solution was washed with water and the aqueous solution was washed with EtOAc (60 mL). The combined organic solutions were washed with brine, dried over MgSO4, filtered, and concentrated. Purification by flash chromatography (CHCl3) provided the title compound (69%) as a gold oil. 1H NMR (400 MHz, CDCl3) δ 6.85 (d, 1H), 6.70 (d, 1H), 5.20 (m, 1H), 4.40 (s, 2H), 3.80 (s, 2H), 3.70 (s, 3H), 2.80 (s, 3H).

후처리

  1. customthe reaction was lowered into a pre-heated water bath at 45° C.
  2. customHCl (g) was bubbled into the solution for 2-3 minutes
  3. customrose to about 60° C
  4. temperatureUpon cooling
  5. customrose to 70° C
  6. stirringThe reaction was stirred for 3 h
  7. washThe organic solution was washed with water
  8. washthe aqueous solution was washed with EtOAc (60 mL)
  9. washThe combined organic solutions were washed with brine
  10. dry with materialdried over MgSO4
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customPurification by flash chromatography (CHCl3)

출처 및 근거

ORD 기록
ord-eb773b7909af47c79e06264d7212ea21
출처 데이터셋
uspto-grants-2003_11
특허 번호
US06649657B2

연결된 노트

불러오는 중…